Lu Zhichao, Furumatsu Takayuki, Fujii Masataka, Maehara Ami, Ozaki Toshifumi
Department of Orthopaedic Surgery, Okayama University Graduate School, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558, Japan.
Department of Orthopaedic Surgery, Okayama University Graduate School, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558, Japan.
J Orthop Sci. 2017 Jul;22(4):715-721. doi: 10.1016/j.jos.2017.02.006. Epub 2017 Mar 18.
The meniscus plays an important role in controlling the complex biomechanics of the knee. Meniscus injury is common in the knee joint. The perimeniscal capillary plexus supplies the outer meniscus, whereas the inner meniscus is composed of avascular tissue. Angiogenesis factors, such as vascular endothelial growth factor (VEGF), have important roles in promoting vascularization of various tissues. VEGF-mediated neovascularization is beneficial to the healing of injured tissues. However, the distribution and angiogenic role of VEGF remains unclear in the meniscus and injured meniscus. We hypothesized that VEGF could affect meniscus cells and modulate the meniscus healing process.
Menisci were obtained from total knee arthroplasty patients. Meniscal injury was created ex vivo by a microsurgical blade. VEGF mRNA and protein expression were detected by the polymerase chain reaction and immunohistochemical analyses, respectively.
In native meniscal tissue, the expression of VEGF and HIF-1α mRNAs could not be detected. However, VEGF and HIF-1α mRNAs were found in cultured meniscal cells (VEGF: outer > inner; HIF-1α: outer = inner). Injury increased mRNA levels of both VEGF and HIF-1α, with the increase being greatest in the outer area. Immunohistochemical analyses revealed that VEGF protein was detected mainly in the outer region and around injured areas of the meniscus. However, VEGF concentrations were similar between inner and outer menisci-derived media.
This study demonstrated that both the inner and outer regions of the meniscus contained VEGF. HIF-1α expression and VEGF deposition were high in injured meniscal tissue. Our results suggest that injury stimulates the expression of HIF-1α and VEGF that may be preserved in the extracellular matrix as the healing stimulator of damaged meniscus, especially in the outer meniscus.
半月板在控制膝关节复杂的生物力学方面发挥着重要作用。半月板损伤在膝关节中很常见。半月板周围毛细血管丛供应半月板外侧，而内侧半月板由无血管组织构成。血管生成因子，如血管内皮生长因子（VEGF），在促进各种组织的血管化过程中发挥重要作用。VEGF介导的新生血管形成有利于受损组织的愈合。然而，VEGF在半月板及损伤半月板中的分布和血管生成作用仍不清楚。我们推测VEGF可能影响半月板细胞并调节半月板愈合过程。
从全膝关节置换术患者中获取半月板。通过显微手术刀片在体外造成半月板损伤。分别采用聚合酶链反应和免疫组织化学分析检测VEGF mRNA和蛋白表达。
在天然半月板组织中，未检测到VEGF和HIF-1α mRNA的表达。然而，在培养的半月板细胞中发现了VEGF和HIF-1α mRNA（VEGF：外侧>内侧；HIF-1α：外侧=内侧）。损伤增加了VEGF和HIF-1α的mRNA水平，在外周区域增加最为明显。免疫组织化学分析显示，VEGF蛋白主要在半月板的外侧区域和损伤区域周围检测到。然而，内侧和外侧半月板来源的培养基中VEGF浓度相似。
本研究表明半月板的内侧和外侧区域均含有VEGF。在损伤的半月板组织中HIF-1α表达和VEGF沉积较高。我们的结果表明损伤刺激了HIF-1α和VEGF的表达，它们可能作为受损半月板的愈合刺激因子保留在细胞外基质中，尤其是在外侧半月板。
